Methamphetamine use disorders and treatment admissions have markedly increased over the past decade. Currently, there are no specific pharmacological treatments available for methamphetamine use disorders. The search for successful methamphetamine pharmacotherapies has been hampered, in part, because of the lack of available data assessing a broad range of methamphetamine-related effects in humans. Of the few studies conducted with human research volunteers, most have employed the oral route of administration (a route least often associated with abuse), and only one study has assessed the effects of methamphetamine via the intranasal route (a route commonly associated with abuse). In the proposed research, we will carefully evaluate the cardiovascular, subjective, and other behavioral effects of intranasal methamphetamine, correlating these effects with methamphetamine plasma levels. Then, we will use a laboratory model of drug self-administration to fully characterize the reinforcing effects of methamphetamine. Finally, we will evaluate the ability of gabapentin, a g-aminobutyric acid (GABA) agonist, and bupropion, a monoamine transporter inhibitor to modify the reinforcing and subjective effects of methamphetamine. The aims of the proposed studies are to: 1) correlate the cardiovascular, subjective, and other behavioral effects of a range of doses of intranasal methamphetamine with methamphetamine plasma levels;2) develop a laboratory model of intranasal methamphetamine self-administration by humans;and 3) investigate the effects of gabapentin maintenance on the reinforcing and subjective effects of intranasal methamphetamine. The strength of this application lies in employing divergent techniques to generate a database examining the effects of intranasal methamphetamine in humans, and thereby contributing to a more comprehensive understanding of methamphetamine use disorders and treatment.